This revised competing renewal builds on the success of the COBRE Center for Cancer Research Development (CCRD) in guiding promising junior investigators towards independence. The External Advisory and Senior Faculty Mentoring and Advisory Committees (EAC and SFMAC) will play essential roles in mentoring of junior investigators. The Proteomics and Molecular Pathology Cores will continue to provide advanced technologies and expert guidance, assets that enhance competitiveness for extramural funds. Recognizing the high cancer mortality in Rhode Island, CCRD will continue to support hypothesis driven research in the area of GI Cancer. Development of new collaborative endeavors focused on stem cells in liver/GI cancer will be overseen by a Research Development Committee. This theme will take full advantage of the strong liver and stem cell research programs already ongoing at Rhode Island Hospital. Five talented investigators with overlapping research interests will generate opportunities for sharing of ideas and productive interaction. Dr. Chin will examine the role of acetylation dependent STATS signaling pathways in self-renewal and metastasis of cancer stem cells in human and rat hepatocellular carcinomas. Dr. Chatterjee, an investigator who joined CCRD in year 5, will focus on raf kinase inhibitory protein (RKIP), a potential biomarker for susceptibility to chemotherapy and an inhibitor of STAT3 mediated metastasis of human colon cancer. Dr. Sanders, a new investigator, will examine the mitogenic signaling phenotype of bipotent hepatic progenitors isolated from fetal and adult liver and how these pathways are influenced by the adult liver microenvironment. Dr. Altura, another new investigator will examine the role that acetylation plays in the localization, dimerization and activity of survivin as a regulator of cell division and an inhibitor of apoptosis. Dr. Moss, a CCRD supported investigator with his first RO1, will pursue a new line of research centered on gastrokine-1/2, two novel tumor suppressor genes identified during his first cycle of COBRE funding. Although expanding basic cancer research will continue to be the primary mission of CCRD, we will work through the Friends of CCRD to increase fundraising efforts and augment outreach activities aimed at increasing public awareness of the value of cancer research. Fostering interactions between basic scientists and clinical oncologists through innovative programs driven by clinical observation will also be a high priority. During the next 5 years, CCRD will expand its leadership role in sustaining a dialogue with State and Federal legislators and policy makers. CCRD will provide the basic research framework needed for transitioning into an NCI designated clinical cancer center.